Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with limited treatment options. The widely distributed plant Aloe vera has shown protective effects against NASH in animals, yet the precise mechanism remains unknown. In this study, we investigated the potential mechanisms underlying the anti-NASH effects of Aloe vera using a network pharmacology and molecular docking approach. By searching online databases and analyzing the Gene Expression Omnibus dataset, we obtained 260 Aloe vera–NASH common targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the common targets were strongly associated with the key pathological processes implicated in NASH, including lipid and glucose metabolism, inflammation, apoptosis, oxidative stress, and liver fibrosis. Four core proteins, AKT serine/threonine kinase 1 (AKT1), tumor necrosis factor alpha (TNFα), transcription factor c-Jun, and tumor suppressor protein p53, were identified from compound–target–pathway and protein–protein interaction networks. Molecular docking analysis verified that the active ingredients of Aloe vera were able to interact with the core proteins, especially AKT1 and TNFα. The results demonstrate the multi-compound, multi-target, and multi-pathway mechanisms of Aloe vera against NASH. Our study has shown the scientific basis for further experiments in terms of the mechanism to develop Aloe vera-based natural products as complementary treatments for NASH. Furthermore, it identifies novel drug candidates based on the structures of Aloe vera’s active compounds.